AB0040 DIFFERENCIALLY EXPRESSED GENES IN PATIENTS WITH OSTEOARTHRITIS
Authors: R. Martinez, C. Elizondo Solis, A. Montoya Rosales, M. Salinas Carmona, N. Macias-Segura
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Osteoarthritis (OA) is a chronic degenerative disease that affects the joints, causing symptoms of arthralgias, swelling, loss of flexibility, etc. It is the most common rheumatic disease with an estimate of 27 million patients in the US [2]. Its pathophysiology is not yet well understood, as it is thought to be a result of multiple factors that induce metalloproteases, synovial angiogenesis and inflammatory cytokines that leads to inflammation and cartilage destruction [3]. To better understand the molecular mechanisms underlying this disease, we performed a meta-analysis with integrative bioinformatics. <h3>Objectives</h3> We aimed to obtain and assess overlapped differentially expressed genes (DEGs) in datasets of patients with OA through functional enrichment and protein-protein interactions (PPI). <h3>Methods</h3> We designed a search strategy in the Gene Expression Omnibus platform to identify datasets of gene expression profiling by array of patients with osteoarthritis. The inclusion criteria were: 1) Presence of healthy controls in the datasets, and 2) Analysis of data with GEO2R. The exclusion criteria were: 1) Incomplete information in the datasets, 2) Failure to identify case and controls, and 3) Gene expression by RNAseq. DEGs were selected when <i>p</i> &lt; 0.05 and Logfold change &gt; 2. We assessed the genes with DAVID database, and PPI through String and Cytoscape; and performed a prediction analysis of possible therapeutic targets. <h3>Results</h3> 6 datasets fulfilled the inclusion criteria, and 128 overlapped DEGs were identified. DAVID database yielded the top 3 Biological Processes involving those genes (Table 1). Cytoscape detected 3 clusters in which those genes interact, and iRegulon proposed CHD1 gene as a possible therapeutic target to regulate the entire cluster (Figure 1). <h3>Conclusion</h3> We aimed to identify and assess DEGs involved Osteoarthritis pathophysiology, as well as predict a possible therapeutic target. Our results suggest that immune processes involving B-cell activation and phagocytosis, as well as complement activation underlie OA pathophysiology. Validation of these results in patients with OA is needed since they can serve as possible diagnostic biomarkers. Further research is necessary to analyze the other clusters, and CHD1 characterization as a possible therapeutic target. <h3>References</h3> [1]Jang, Sunhee et al. "Recent Updates of Diagnosis, Pathophysiology, and Treatment on Osteoarthritis of the Knee." International journal of molecular sciences vol. 22,5 2619. 5 Mar. 2021, doi:10.3390/ijms22052619 [2]Hamilton, John L et al. "Targeting VEGF and Its Receptors for the Treatment of Osteoarthritis and Associated Pain." Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research vol. 31,5 (2016): 911-24. doi:10.1002/jbmr.2828 [3]Abramoff, B., &amp; Caldera, F. E. (2020). Osteoarthritis: Pathology, Diagnosis, and Treatment Options. The Medical clinics of North America, 104(2), 293–311. https://doi.org/10.1016/j.mcna.2019.10.007 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.